The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for tezepelumab for the treatment of patients with severe asthma.
Tezepelumab is an investigational first-in-class human monoclonal antibody that works by blocking thymic stromal lymphopoietin, an epithelial cytokine involved in the initiation and persistence of airway inflammation.The BLA submission is supported by data from the PATHFINDER clinical program, which includes the phase 3 NAVIGATOR trial (ClinicalTrials.gov Identifier: NCT03347279).
The double-blind, placebo-controlled study assessed the efficacy and safety of tezepelumab in 1061 patients 12 to 80 years of age with severe, uncontrolled asthma who were receiving medium- or high-dose inhaled corticosteroid plus at least 1 additional controller medication with or without oral corticosteroid. The study included patients with both high and low blood eosinophil counts.
Patients were randomly assigned 1:1 to receive tezepelumab or placebo administered by subcutaneous injection, in addition to standard of care. The primary end point was the annualized asthma exacerbation rate during the 52-week treatment period.
Results showed that treatment with tezepelumab was associated with a statistically significant and clinically meaningful 56% reduction in annualized asthma exacerbation rate in the overall patient population compared with placebo (0.93 [95% CI, 0.80-1.07] vs 2.10 [95% CI, 1.84-2.39]; rate ratio, 0.44 [95% CI, 0.37-0.53]; P >.001). A significant and clinically meaningful 41% reduction in annualized asthma exacerbation rate was also observed in tezepelumab-treated patients with baseline eosinophil counts less than 300 cells/µL (1.02 [95% CI, 0.84-1.23] with tezepelumab vs 1.73 [95% CI, 1.46-2.05] with placebo; rate ratio, 0.59 [95% CI, 0.46-0.75]; P <.001). Similar reductions were seen in patients with baseline eosinophil counts less than 150 cells/µL.
Tezepelumab also met key secondary endpoints resulting in significant improvements in lung function, asthma control and quality of life. As for safety, the most frequently reported adverse events with tezepelumab were nasopharyngitis, upper respiratory tract infection and headache.
“Tezepelumab has demonstrated reductions in exacerbations irrespective of blood eosinophil counts, allergy status and fractional exhaled nitric oxide, and has the potential to transform treatment for a broad population of severe asthma patients,” said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D. “This decision brings us a step closer to delivering a much-needed, first-in-class medicine for asthma patients, many of whom remain uncontrolled and at risk of asthma attacks despite the availability of inhaled and biologic medicines.
A Prescription Drug User Fee Act (PDUFA) target date for the first quarter of 2022 has been set for the application. The FDA previously granted Breakthrough Therapy designation to tezepelumab for this indication.
- Tezepelumab regulatory submission accepted and granted FDA Priority Review in the US for the treatment of patients with asthma. [press release]. Wilmington, DE: AstraZeneca; July 8, 2021.
- Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. Published online May 13, 2021. doi: 10.1056/NEJMoa2034975